1. Field
This invention is concerned generally with blood collection test tubes or devices which are ultimately used to separate whole blood into serum and clot portions to facilitate analysis of the blood. Specifically, the invention is concerned with an improved gel-like composition which can be used in such blood collection tubes. Such compositions have physical and chemical properties which, in the presence of whole blood, permit the composition to be centrifuged to a position intermediate that of the serum and clot portions and, hence, form a barrier between the two portions.
2. Prior Art
Although the specific gravity of whole human blood is generally within the range of about 1.048 to 1.066, it has long been known that such blood can be readily centrifuged to effect a separation of the blood into two major components--a lighter serum portion having a specific gravity within the range of about 1.026 to 1.031 and a heavier clot portion, consisting mainly of red blood cells, having a specific gravity within the range of about 1.092 to 1.095. Such separations of whole blood into its two major components have greatly facilitated physical and chemical analyses of blood and, hence, assisted in the diagnosis and prognosis of many human ailments.
With the advent of modern sophisticated techniques for the analysis of various physical and chemical sub-components of blood, there has been a general recognition that simple centrifugation of whole blood into its two major components does not necessarily effect an ideal separation for analytical purposes. For example, even though simple centrifugation yields a gross separation of whole blood into serum and clot portions, there still exists an interface between the separated portions which, especially with time, results in the diffusion of various sub-components of one separated portion into the other. Such diffusion can affect the accuracy of various analyses.
In recent years, efforts have been made to overcome the problems associated with simple centrifugation. For example, it is now well known that various materials or devices having a specific gravity between those of the serum and clot portions can be used to assist in the separation and partitioning of the serum and clot portions. One such material consists of a gel-like, relatively inert, viscous composition having a specific gravity within the range of about 1.030 to about 1.050. Typical components of such a composition are a silicone fluid and a particulate silica filler. When whole blood, contained, for example, in a test tube, is centrifuged in the presence of such a composition, the composition, because of its specific gravity, tends to migrate to a position intermediate those of the serum and clot portions. Because of their viscous nature, such compositions ultimately assume a configuration which discourages and prevents formation of a serum-clot interface, thereby forming a physical and chemical barrier between the serum and clot portions.
Various examples of such silica-silicone fluid compositions are well known in the art and described in detail, for example, in U.S. Pat. No. 3,780,935 to Lukacs and Jacoby and U.S. patent application Ser. No. 314,270, cited above, and incorporated herein by reference thereto. In the above cited patent and patent application, preferred compositions consist essentially of two components--a silicone fluid such as a dimethylpolysiloxane and very fine silica particles which act as a filler to assist in forming a gel-like material having an appropriate specific gravity. Such components tend to be preferred because they are essentially inert and, in combination, permit control of both specific gravity and viscosity.
In using such two component compositions, however, it has been found that, in time, the silicone fluid (e.g., a dimethylpolysiloxane) tends to react completely with the surfaces of the silica particles. This can result in a "wet out" of the particles. Very generally, the expression "wet out" refers to the tendency of such compositions to lose viscosity with time. Such a loss or reduction of viscosity leads to a reduction of the gel-like nature of the composition and the relative firmness of the composition is lessened. A very undesirable effect of wet out occurs when an attempt is made to pour off the upper serum portion of separated blood contained in a test tube. For example, as long as the test tube containing the separated blood components (with the gel-like barrier between) is maintained in an essentially vertical position, wet out poses no particular problem. However, as the tube is tilted to pour off the serum portion, a wetted out barrier has a tendency to slump, thus disturbing the previously maintained seal between the serum and clot portions. As the seal is disturbed, there forms an interface between the serum and clot portions. Since such an interface permits diffusion or migration of various sub-components of the serum or clot portion into the other portion, the accuracy of various analyses can be adversely affected. It should be noted that undesirable slumping of the seal can occur even if a test tube containing such a seal between separated portions is jarred. From the foregoing, it can be appreciated that wet out of gel-like blood separating barriers is undesirable and the possibility of wet out occurring is a severe limitation on the storage stability of such gel-like compositions, whether stored in bulk or in individual evacuated blood collection containers.
It is known that such silicone fluid-silica compositions can be stabilized to some extent by adding such third components as glycerol or even water. Both compounds have hydroxyl groups which tend to compete with the silicone fluid for surface bonding sites on the silica particles, thus tending to preclude the complete reaction of the silica surfaces with the silicone fluid which tends to result in wet out. It can be appreciated, however, that such compounds as glycerol and water are relatively small molecules which are not necessarily good network formers which assist in spacing individual silica particles apart from one another. Further, such compounds are not necessarily essentially inert with respect to the various sub-components of blood.
I have now found that there exists a group of compounds which, when added in relatively small amounts to a silicone fluid-silica gel-like composition, prolong the storage stability of such compositions and minimize the occurrence of wet out. The discovery is rather surprising since these third-component compounds have been used in entirely different applications in the past -- as surfactants in the preparation of polyurethane foams. The compounds (copolymers) and their use are described in detail below.